Professor McCluskey's research career began as a medical student when he worked in the All Africa Leprosy Rehabilitation and Training Center (ALERT, now All Africa Leprosy, Tuberculosis and Rehabilitation Training Centre) in Addis Ababa, Ethiopia then trained in Perth as a physician working briefly as a Flying Doctor in the WA Kimberley region and an intern at Kalgoorlie Hospital. He studied for four years at the National Institutes of Health (USA). He subsequently held academic positions at Monash University, Flinders University and the Australian Red Cross Blood Service in Adelaide, South Australia where he headed transplant services and established the SA unrelated bone marrow donor registry. At The University of Melbourne he has held senior positions and has been Deputy Vice Chancellor Research since 2011.
He has published more than 300 scientific articles on how genes control immunity, recognised by the Parr Prize from the Australian Rheumatism Association, the Priscilla Kincaid Smith Oration and medal of the Royal Australian College of Physicians, the Rose Payne Award from the American Society for Histocompatibility and Immunogenetics (ASHI), The Ceppellini award from the European Federation for Immunogenetics, the International Roche Organ Transplantation Fund Recognition Prize for Excellence in Organ Transplantation Research jointly with Jamie Rossjohn, an Australian Museum Eureka award for scientific Research (McCluskey, Kjer-Nielsen and Rossjohn) and NHMRC Research Excellence Award for top NHMRC Program Grant in 2012. He received GSK Research Excellence Award and the 2016 Victoria Prize for Life Sciences (both jointly with Jamie Rossjohn).
In 2010 he was elected to the Faculty of Science, Royal College of Pathologists Australasia. He is a Fellow Australian Academy of Science, Fellow of the Australian Academy of Health and Medical Sciences, Fellow of the Royal Australian College of Physicians and Fellow of the Royal College of Pathologists Australasia.